Infection continues to be a leading cause of illness and death in human neonates, suggesting an immaturity of the host defense system. Although previous studies have established that the newborn neutrophil functions inefficiently, most investigations have focused on in vitro phenomena such as chemotaxis and bactericidal function. In this laboratory we have examined other components of the neonatal neutrophil life cycle in vivo and have found a number of them to be either defective or sluggish (but not absent or completely defective) in response to established stimuli. For example, in our animal model lithium stimulation of granulocytopoeisis is persistently depressed in neonates, while neutrophil release from the marrow pool after endotoxin challenge and neutrophil recruitment to focal sites of infection are both kinetically indolent. The objectives of this proposal are: 1) to quantitate the kinetics of neutrophil movement in both neonates and adults from marrow to vascular space to focal sites using radiolabeling techniques both in the baseline, steady-state and following the stimulus of focal inflammation; 2) to elucidate mechanisms of the abnormal neutrophil functions, which we have already described, by examining a) the role of colony-stimulating factor in defective granulocytopoeisis, b) the role of granulocyte-releasing factor in the indolent release of neutrophils from the marrow pool and c) the role of plasma membranes in indolent neutrophil migration to focal sites using several biological probes to characterize membrane structure and function; and finally 3) to study other previously unexamined components of the neonatal neutrophil life cycle including margination-demargination using epinephrine challenge. These studies will establish an animal model basis for quantitative characterization of host compromise in human neonates and will provide for future experiments to examine the role of immunopotentiating agents in the amelioriation of infection in the neonate.